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INNOVATIONS IN CARDIOVASCULAR RISK IN THE LAST YEAR. A EUROPEAN PERSPECTIVE

INNOVATIONS IN CARDIOVASCULAR RISK IN THE LAST YEAR. A EUROPEAN PERSPECTIVE. The FL Chapter ACC Annual Meeting Orlando, August 17, 2013. Vicente Bertomeu Martínez Head of Cardiology. Hospital Universitario San Juan de Alicante (Spain)

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INNOVATIONS IN CARDIOVASCULAR RISK IN THE LAST YEAR. A EUROPEAN PERSPECTIVE

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  1. INNOVATIONS IN CARDIOVASCULAR RISK IN THE LAST YEAR.A EUROPEAN PERSPECTIVE The FL Chapter ACC Annual Meeting Orlando, August 17, 2013 • Vicente Bertomeu Martínez • Head of Cardiology. Hospital Universitario San Juan de Alicante (Spain) • Prof. of Cardiology UCAM. Director International Institute of Cardiology • President Spanish Society of Cardiology

  2. Decrease in deaths from coronary heart disease attributed to treatments versus prevention VBM 2013

  3. VBM 2013

  4. VBM 2013

  5. VBM 2013

  6. Cardiovascular age VBM 2013

  7. HYPERTENSION

  8. ESH/ESC 2013 Hypertension guidelines Historical perspecive Guías 2003 Guías 2007 Revisión ESH 2009 Guías 2013 J Hypertens 2013;31:1281-1357 Eur Heart J 2013 Blood Pressure 2013 VBM 2013

  9. JNC VII: Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling Indications With Compelling Indications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Stage 1 Hypertension(SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 Hypertension(SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist. VBM 2013

  10. ESH/ESC 2013 Hypertension guidelines Stratification of total CV risk in categories of low, moderate, high and very high risk VBM 2013

  11. ESH/ESC 2013 Hypertension guidelines Blood Pressure Measurements • Office or clinic Blood Pressure • Out-of-office Blood Monitoring Pressure • Ambulatory Blood Pressure Monitoring (ABPM) • Home Blood Pressure Monitoring (HBPM) VBM 2013

  12. VBM 2013

  13. ESH/ESC 2013 Hypertension guidelines Blood Pressure treatment tarjets • SBP < 140 mmHg, independently of the risk • Low-to-moderate risk hypertensive patients(IB) • Diabetes (IA) • CKD (IIaB) • Previous cardiovascular events (IIaB) • PAD < 90 mmHg VBM 2013

  14. Objetivos del Tratamiento. Guías ESC-ESH 2007 140/90 mmHg o cifras inferiores si son toleradas, en todos los hipertensos. < 130/80 mmHg en diabéticos y pacientes de alto ó muy alto riesgo: Ictus Enf. Coronaria Enfermedad Renal Crónica Proteinuria J Hypertens 2007; 25: 1.105-1.187 VBM 2013

  15. Adjusted risk of outcome events by achieved SBP divided into deciles. ONTARJET Sleight, et al . J. Hypertens 2009;27:1360-69 VBM 2013

  16. Adjusted relationship between tertiles of changes in SBP within each quartile of baseline SBP on the primary outcome Quartile 1 : Baseline SBP <130 mmHg ³ Tertile 1: Increase by 10 mmHg Tertile 2: Increase by 0 - 10 mmHg Tertile 3: Decrease in BP Quartile 2 : Baseline SBP 131 - Tertile 1: No change or increase in BP Tertile 2: Decrease by 1 9 mmHg Tertile 3: Decrease > 9 mmHg Quartile 3 : Baseline SBP 143 - 154 mmHg Tertile 1: Decrease ? 6 mmHg Tertile 2: Decrease 6 Tertile 3: Decrease > 15 mmHg : Baseline SBP > 154 mmHg Tertile 1: Decrease Tertile 2: Decrease 13 Tertile 3: Decrease > 24 mmHg Reduced Reduced Increased Increased Risk Risk Risk Risk Quartile 1 Quartile 1 : Baseline SBP : Baseline SBP p value p value P for P for HR (96% CI) HR (96% CI) trend trend ³ ³ Tertile 1: Tertile 1: Increase by Increase by 10 mmHg 10 mmHg 1 1 - - Tertile 2: Increase by 0 Tertile 2: Increase by 0 10 mmHg 10 mmHg 1.04 1.04 (0.89 (0.89 1.22) 1.22) 0.599 0.599 - - 0.050 0.050 Tertile 3: Decrease in BP Tertile 3: Decrease in BP 1.19 1.19 (1.01 (1.01 1.40) 1.40) 0.042 0.042 - - - - Quartile 2 Quartile 2 : Baseline SBP 131 : Baseline SBP 131 142 mmHg Tertile 1: No change or increase in BP Tertile 1: No change or increase in BP 1 1 Tertile 2: Decrease by 1 Tertile 2: Decrease by 1 - 0.81 0.81 (0.69 (0.69 0.95) 0.95) 0.010 0.010 - - 0.364 0.364 Tertile 3: Decrease > 9 mmHg Tertile 3: Decrease > 9 mmHg - - 0.94 0.94 (0.80 (0.80 1.10) 1.10) 0.415 0.415 143 143 - - 154 154 Quartile 3 Quartile 3 : Baseline SBP : Baseline SBP mmHg mmHg Tertile 1: Decrease Tertile 1: Decrease 6 mmHg 6 mmHg ? ? 1 1 Tertile 2: Decrease 6 Tertile 2: Decrease 6 15 mmHg - 0.76 0.76 (0.65 (0.65 0.88) 0.88) 0.0003 0.0003 - - 0.0001 0.0001 Tertile 3: Decrease > 15 mmHg Tertile 3: Decrease > 15 mmHg 0.74 0.74 (0.63 (0.63 0.87) 0.87) 0.0002 0.0002 - - Quartile 4 : Baseline SBP : Baseline SBP 154 mmHg 154 mmHg > > Tertile 1: Decrease Tertile 1: Decrease <13 mmHg 1 1 Tertile 2: Decrease 13 Tertile 2: Decrease 13 -24 mmHg - - 0.80 0.80 (0.69 (0.69 0.92) 0.92) 0.002 0.002 0.0001 0.0001 Tertile 3: Decrease > 24 mmHg Tertile 3: Decrease > 24 mmHg 0.73 0.73 (0.63 (0.63 0.86) 0.86) <0.001 <0.001 - - 0.2 0.2 0.6 0.6 1.0 1.0 1.2 1.2 1.6 1.6 0.4 0.4 0.8 0.8 1.4 1.4 Sleight, et al . J. Hypertens 2009;27:1360-69 VBM 2013

  17. ESH/ESC 2013 Hypertension guidelines Elderly Hypertensives VBM 2013

  18. Guía de hipertensión ESH/ESC 2013 Choice of antihypertensive drug • The main benefits of antihypertensive treatment are due to lowering of BP “per se”. • Reconfirm that: • Diurétics • Beta blockers • Calcium Antagonist • Angiotensin-converting enzyme (ACE) inhibitors • Angiotensin receptor blockers (ARAII) • Are all suitable for the initiation and maintenance, either as monotherapy or in some combinations VBM 2013

  19. ESH/ESC 2013 Hypertension guidelines Possible Combinations Green continuous line: Preferred Green dashed line: Usseful (with limitations) Black dashed line: Posible but less tested Red continuous line: Not recomended VBM 2013

  20. ESH/ESC 2013 Hypertension guidelines Strategies in Resistant Hypertensión VBM 2013

  21. DISLIPEMIA VBM 2013

  22. DISLIPEMIA • Parameters to be measured: CT, LDL, TG y HDL. • Main objective: LDL. • Very high-risk patients: <70 mg/dl (level of evidence in IA) . • High-risk patients: <100 mg/dl (IIaA). • Moderate-risk patients: <115 mg/dl (IIaC). Reduction of at least 50% of basal levels VBM 2013

  23. Statins are the most effective drugs for the lowering of total cholesterol and LDL. • For every ↓ of 40 mg/dl of LDL the morbidity and mortality levels are reduced by 22%. VBM 2012

  24. N Engl J Med. 2011 Nov 15. VBM 2013

  25. About the HPS2-THRIVE trial The addition of the combination of nicotinic acid of modified release and laropiprant to the treatment of statins produced no additional significant reduction in the risk of combined deaths from coronary heart disease, non-fatal heart failures, ictus or revascularizations when compared to statin therapy. There was also a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received nicotinic acid of modified release and laropiprant. MSD recommends that doctors stop prescribing TREDAPTIVE. MSD also recommends that, in due course, doctors review the treatment plans of patients that are taking TREDAPTIVE stopping treatment with TREDAPTIVE VBM 2013

  26. Intima-Media Thickness of the Carotid Artery during 24 and 14 Months of Therapy ENHANCE-Trial The results of the IMPROVIT trial which will be available in 2015, should finally put an end to this problem. ARBITER-6 HALTS Kastelein J et al. N Engl J Med 2008;358:1431-1443 Taylor A et al. N Engl J Med 2009;361:2113-2122 VBM 2011

  27. Level of LDL-C and CV eventsLower is Better ??? 30 4S - Placebo 25 Secondary prevention 4S - Rx 20 LIPID - Placebo Rate of events (%) 15 CARE - Placebo LIPID - Rx CORONA - Placebo CARE - Rx Primary prevention CORONA - Rx HPS - Placebo TNT – ATV10 HPS - Rx 10 PROVE-IT - PRA WOSCOPS – Placebo TNT – ATV80 AFCAPS - Placebo PROVE-IT – ATV 6 5 AFCAPS - Rx WOSCOPS - Rx ASCOT - Placebo ASCOT - Rx 0 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) 200 (5.2) LDL-C mg/dL (mmol/L) Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279 LaRosa JC et al. N Engl J Med 2005;352:1425-1435 VBM 2012

  28. Level of LDL-C and CV events 30 4S - Placebo 25 Secondary prevention 4S - Rx 20 LIPID - Placebo Rate of events (%) 15 CARE - Placebo LIPID - Rx CORONA - Placebo CARE - Rx Primary prevention CORONA - Rx HPS - Placebo TNT – ATV10 HPS - Rx 10 PROVE-IT - PRA WOSCOPS – Placebo TNT – ATV80 AFCAPS - Placebo PROVE-IT – ATV 6 5 AFCAPS - Rx WOSCOPS - Rx ASCOT - Placebo ASCOT - Rx 0 40 (1.0) 60 (1.6) 80 (2.1) 100 (2.6) 120 (3.1) 140 (3.6) 160 (4.1) 180 (4.7) 200 (5.2) LDL-C mg/dL (mmol/L) Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279 LaRosa JC et al. N Engl J Med 2005;352:1425-1435 VBM 2012

  29. Patients receiving statins, despite having a low LDL level, had lower rates of major cardiac events • Patients post-STEMI with LDL <70 mg/dl. Most probably the benefits lies in the use of statin and not in the level of LDL HK Lee et al. Benefit of early statin therapy in patients with acute myocardial infarction who have extremely low low-density lipoprotein cholesterol. J Am Coll Cardiol 2011;58:1664-1671. VBM 2012

  30. Benefits of statin therapy in patients with acute coronary syndrome Mortality from any cause • cLDL >70 mg/dl • cLDL <70 mg/dl Cumulative survival rate Statin Non-Statin • HR: 0,09 (IC 95% 0,05-0,17); p<0,01 • HR: 0,19 (IC 95% 0,08-0,44); p<0,01 Cordero A, Bertomeu V, et al. Rev Esp Cardiol 2013 VBM 2013

  31. HDL: principal determinante del SCA Determinantes bioquímicos de SCA vs. DT no isquémico Cordero A, Bertomeu V, et al. Rev Esp Cardiol; 2012:65:319-25 VBM 2013

  32. 2.HDL-c: Inhibición de CETP CETP Dalcetrapid Anacetrapid Evacetrapid VBM 2013

  33. 2.HDL-c: Inhibición de CETP VBM 2013

  34. LDL-c: Inhib. Degradación LDL-R Ausencia de PCSK9 Presencia de PCSK9 • Menos LDL-Receptor • LDL-C sérico alto • Más LDL-Receptor • LDL-C sérico bajo Abifadel M, et al. Nature Genet 2003; 34:154-156 VBM 2013

  35. LDL-c: Inhib. Degradación LDL-R Cambio en LDL-c en 12 semanas Buttheymustprovethatthereisalso a reduction in themorbidity and mortalityrates Stein EA, et al. NEJM 2012;366:1108-18 VBM 2013

  36. TOBACCO VBM 2013

  37. Tobacco and STEMI No Smokers 423 (51,2%) 401 (49,8%) 17 exfumadores <1año (4,2%) Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013

  38. Differences between groups Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 20123

  39. p<0,01 Risk Profile 170 160 • 150,3 (30,6) • 146,2 (30,9) GRACE score ] 150 ] 140 • 132,1 (30,1) ] 130 Non Smokers Exsmokers Smokers Cordero A, Bertomeu v, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013

  40. Risk Profile • 86,1 (24,0) • 87,1 (25,0) • 85,2 (24,0) 90,00 ] ] GRACE score Without age ] 85,00 80,00 The risk in smokers is the same as that of non smokers who are 10 years older • p=0,3 Non smokers Exsmokers Smokerss Cordero A, Bertomeu V, et al. Med Clin (Barc) 2012; 138:422-28 VBM 2013

  41. Trends in Mortality From Myocardial Infarction. A Comparative Study Between Spain and the United States: 1990-2006Domingo Orozco-Beltrana, Richard S. Cooperb, Vicente Gil-Guillena, Vicente Bertomeu-Martinezc, Salvador Pita-Fernandezd, Ramón Durazo-Arvizub, Concepción Carratala-Munueraa, Luis Cea-Calvoa, Vicente Bertomeu-Gonzalezc,, Teresa Seoane-Pilladoc, Luis E. Rosadoe USA shows better results. Probably better implementations of Therapeutic Procedures and to having an effective and preventive policy against risk factors Rev Esp Cardiol. 2012;65:1079-85 VBM 2013

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